Of impurities, drugs and metabolites - ToF-SIMS application studies for use in the pharmaceutical sciences

This thesis aims to explore the use of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for applications in the pharmaceutical sciences through three separate studies with different pharmaceutical applications. The first study investigated the use of ToF-SIMS for the surface characterisation of pharmaceutical crystals using 4-nitrophenol and 4-acetamidobenzoic acid impurity incorporations in acetaminophen (paracetamol) crystals. A range of impurity deposition scenarios were examined to study the impurity intensity and distribution patterns as well as impurity-induced changes to the crystal surfaces. In the second study, the characteristics of human coronary artery endothelial cells (HCAECs) before and after application of an anti-thrombotic drug were analysed using ToF-SIMS. A sample preparation method was developed to analyse the cells as well as identify and image the drug on the cell surface. Subsequently, untreated and treated cells were prepared using the trialled procedure to investigate the effects of the drug on the cells. The final study explored the use of ToF-SIMS for bacterial analysis, in particular agar-based bacteria and the tracking of bacterial metabolites. In this scenario, various sample preparation and drying methods were trialled and the most successful method applied to attempt the identification and tracking of tetracycline, a known streptomyces metabolite and antibiotic, in the bacterial growth medium. In addition to the ToF-SIMS experimental studies, a software tool for the selection of spectral pre-processing methods for NIR and other spectral applications was developed and assessed. The software toolbox enables a design-of-experiment-centred approach to selecting viable pre-processing methods to correct spectral data prior to further usage in applications such as regression modelling. Two data use-cases are presented that stem from the chemical and pharmaceutical sciences and demonstrate the applicability of the tool.This thesis aims to explore the use of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for applications in the pharmaceutical sciences through three separate studies with different pharmaceutical applications. The first study investigated the use of ToF-SIMS for the surface characterisation of pharmaceutical crystals using 4-nitrophenol and 4-acetamidobenzoic acid impurity incorporations in acetaminophen (paracetamol) crystals. A range of impurity deposition scenarios were examined to study the impurity intensity and distribution patterns as well as impurity-induced changes to the crystal surfaces. In the second study, the characteristics of human coronary artery endothelial cells (HCAECs) before and after application of an anti-thrombotic drug were analysed using ToF-SIMS. A sample preparation method was developed to analyse the cells as well as identify and image the drug on the cell surface. Subsequently, untreated and treated cells were prepared using the trialled procedure to investigate the effects of the drug on the cells. The final study explored the use of ToF-SIMS for bacterial analysis, in particular agar-based bacteria and the tracking of bacterial metabolites. In this scenario, various sample preparation and drying methods were trialled and the most successful method applied to attempt the identification and tracking of tetracycline, a known streptomyces metabolite and antibiotic, in the bacterial growth medium. In addition to the ToF-SIMS experimental studies, a software tool for the selection of spectral pre-processing methods for NIR and other spectral applications was developed and assessed. The software toolbox enables a design-of-experiment-centred approach to selecting viable pre-processing methods to correct spectral data prior to further usage in applications such as regression modelling. Two data use-cases are presented that stem from the chemical and pharmaceutical sciences and demonstrate the applicability of the tool

Des sources du savoir aux médicaments du futur

L'origine des pharmacopées traditionnelles L'élaboration des pharmacopées Les médicaments du XXIe siècle Comment les connaissances des savoirs thérapeutiques se sont-elles transmises au travers des différentes cultures ? Cet ouvrage innovant, qui réunit les travaux présentés au 4e Congrès européen d'ethnopharmacologie, fait remonter à la préhistoire les sources des connaissances thérapeutiques. Si les pharmacopées écrites jalonnent l'histoire des grandes médecines savantes, d'autres modes d'accès à la connaissance semblent exister dans l'univers chamanique des sociétés de tradition orale ainsi que dans la façon dont les animaux malades se soignent par les plantes. L'évaluation des propriétés pharmaco-toxicologiques et chimiques des plantes d'usage traditionnel devrait par ailleurs favoriser le développement futur des médicaments à base de plantes, l'un des thèmes porteurs abordés dans cet ouvrage. Mais l'objectif de ce livre est aussi de susciter, partout dans le monde, de nouvelles thématiques de recherche dans le domaine de la préhistoire du médicament et de la compréhension de l'acquisition et de la transmission du savoir. Le développement du phytomédicament non toxique destiné à l'homme et à l'animal figure également parmi les enjeux majeurs de demain.The origin of traditional pharmacopoeias The development of pharmacopoeias The medicines of the XXIth century How have the traditional Therapeutical knowledges been transmited to the différent cultures? This innovating book containing the proceedings of the 4th European Congress of Ethnopharmacology return to prehistory the sources of fherapeutical knowledge and asks how the animals cure themselves with plants. If the printing pharmacopoeias ponctuate the history of learning medicines other way of accessibility to the knowledge seems exist in the world of shaman in society with oral tradition. Ethnopharmacological evaluation of traditional médicinal plant should favour the development of phytomedicine. The purpose of this publication is also to provide dues to scientists in the whole world and help them identify new avenues for research in the field of the prehistory of drugs, for a better understanding of the way knowledge is acquired and then transmitted, and for the development of non-toxic herbal medicines for administration to human and animal beings